Reduced Intensity Conditioning Hematopoietic Cell Transplantation for Pediatric Patients With Hematologic Malignancies at High Risk for Transplant Related Mortality With Standard Transplantation
Summary/Proposal: Reduced Intensity Hematopoietic Cell Transplantation for High-Risk
Relapsed Pediatric Hematologic Malignancies and Patients Ineligible for Standard
Transplantation We propose a phase II trial of reduced intensity conditioning with
Bu/Flu/ATG in pediatric patients with hematologic malignancies at high risk for transplant
related mortality with standard transplantation. Patients qualify based on organ system
dysfunction, active but stable infection, history of previous transplant, or late stage
disease. We plan to enroll 45 patients through the Pediatric Blood and Marrow transplant
Consortium (PBMTC) and anticipate that the outcome of the trial will pave the way for phase
II or III disease specific protocols addressing efficacy of the approach compared to
standard transplant approaches in better risk patients.
Hypothesis High risk pediatric hematologic malignancy patients ineligible for standard
myeloablative HCT undergoing reduced intensity conditioning (RIC) HCT can achieve a
sustained engraftment rate > 90% with a 100day TRM < 30% using either bone marrow or PBSC
from related or unrelated donors. High risk pediatric patients undergoing RIC-HCT using
related or unrelated cord blood can achieve a sustained engraftment rate >80% and a 100d TRM
<30%.
Rationale for Reduced Intensity Approaches in High Risk Patients There are a number
patient-specific risk factors associated with increased transplant related mortality. They
can be broadly placed into three categories: pretransplant organ system dysfunction, active
infections at the time of transplant, and degree of pretransplant therapy (previous
transplants, third or subsequent remission, etc.).
The primary objective of this study is to determine the likelihood of achieving sustained
donor engraftment using reduced intensity conditioning (fludarabine/busulfan/ATG) followed
by hematopoietic cell transplantation (HCT) with either cord blood, bone marrow or
peripheral blood stem cells (PBMTC) in pediatric patients with hematopoietic malignancies
who are at high risk of transplant related mortality (TRM) with myeloablative HCT. Patients
qualify based on organ system dysfunction, active but stable infection, history of previous
transplant or late stage disease. We plan to enroll 45 patients through the Pediatric Blood
and Marrow Transplant Consortium (PBMTC) and anticipate that the outcome of the trial will
pave the way for phase II or III disease specific protocols addressing efficacy of the
approach compared to standard transplant approaches in better risk patients.
Study procedures Patients receive their conditioning regimen consisting of fludarabine,
busulfan, and ATG and then receive their stem cell transplant. Patients receive
immunosuppression consisting of cyclosporine and mycophenolate mofetil. Patients with
persistent or progressive disease may receive donor lymphocyte infusion off protocol.
Interventional
Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Number of High Risk Pediatric Patients With Successful Sustained Donor Engraftments
Assessed donor engraftment in very high risk pediatric patients.
24 months
Yes
Michael Pulsipher, MD
Principal Investigator
Primary Children's Medical Center
United States: Institutional Review Board
HCI12073
NCT00795132
April 2004
July 2009
Name | Location |
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Primary Children's Medical Center | Salt Lake City, Utah 84113-1100 |